The primary olfactory centers in the brains of humans and most other animals are characterized by an array of synaptic modules called glomeruli, which are organized chemotopically such that chemical information about odor is represented spatially among glomeruli. How sensory information about odor stimuli - and especially mixtures of odor compounds at behaviorally relevant blend proportions - is encoded in neural activity, however, within and among glomeruli before being relayed to higher-order brain areas, is still not well understood. Moreover, studies of the processing of those glomerular outputs downstream in the brain are just beginning. This project builds on a firm foundation of experience with an experimentally favorable model system, the olfactory system of Manduca sexta, which is comparable to its mammalian counterpart in organization and function and is advantageous for neurophysiological testing of hypotheses about neural processing of odor information among glomeruli and thereafter downstream in higher-order brain centers. This model system offers the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and brain neurons, and chemically identified, behaviorally relevant odors. It also provides an excellent opportunity to explore neural relationships within and among identified glomeruli and in higher-order brain centers that receive and further process glomerular outputs, in order to analyze how sensory information about odor compounds and natural, behaviorally relevant mixtures is processed. By means of intracellular recording and staining, extracellular multichannel recording, confocal microscopy, chemical analysis of odor mixtures, behavioral studies and pharmacological interventions, we will investigate identified glomeruli of known odor specificity to test the hypotheses that: (1) synchronous activity (i.e. coincident firing) among the output neurons of glomeruli is an important mechanism for encoding behaviorally significant odor mixtures;(2) such synchronous activity depends on stimulation with mixtures of appropriate chemical composition, concentrations, and blend-proportions of odor components;and (3) the resulting synchronous activity of neurons projecting from glomeruli to higher-order centers is detected by target neurons and is important for their activation and for selective behavioral responses to "meaningful" odor mixtures. The proposed research promises to provide new information about the functional roles of and mechanisms underlying coherent activity of neurons in the olfactory pathway and thus to advance our understanding of olfactory modulation of behavior. Moreover, understanding of neural-network mechanisms underlying the central coding of odor information, gained from this work, should yield insights into the functional changes that accompany disorders of olfaction such as parosmias, hyposmia, and anosmia and at the same time aid efforts to control insects, particularly vectors of devastating diseases that profoundly impact human health and welfare. PUBLIC HEALTH RELEVANCE This research on neural processing of olfactory information in the brain of an experimentally favorable insect model system promises to contribute to our understanding of how neural circuits encode features of sensory stimuli that are essential for appropriate modulation of behavior. Moreover, this line of work further benefits human public health because of the importance of insects as vectors of devastating human diseases (which is based on behaviors all of which depend on olfaction) and the fact that our findings will directly inform research on olfactory-guided behaviors of mosquitoes, kissing bugs, biting flies, and other insects of health importance. This research thus will contribute at once to: understanding of the neural mechanisms underlying odor- information coding in order to gain insights into the functional changes that accompany disorders of olfaction such as parosmias, hyposmia, and anosmia;efforts to control harmful insects that impact human health and welfare;and advances in brain science in general.